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Low-risk luminal A breast cancers may not require radiation Tx

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Positive step forward

Given the overall lower rates of local recurrence seen in modern studies after breast-conserving surgery and radiation therapy, coupled with the possibility of being able to more precisely stratify patients on the basis of risk of recurrence with RT, the question of omitting RT in the treatment of patients with early-stage disease once again comes to the forefront. The reanalysis of the prospective Toronto–British Columbia trial by Liu et al. that accompanies this editorial is a positive step forward in this regard.

This study, coupled with the earlier subtype-based analyses, paves the way for other prospective initiatives using the tumor’s biologic identity to select patients with such a low risk of local recurrence that RT can be avoided without adversely affecting survival.

Dr. Jennifer R. Bellon is at the Dana-Farber Cancer Institute, and is with the department of radiation oncology at Harvard Medical School, Boston. These remarks are taken from an editorial accompanying the study by Dr. Liu and associates (Journ. Clin. Onc. 2015 May 11 [doi:10.1200/JCO.2015.61.2069]).


 

References

Some women with the luminal A subtype of breast cancer appear to be at low risk of relapse and may not need breast radiotherapy, the results of a retrospective analysis suggested.

Among 501 patients with tissue blocks that were retrospectively analyzed for breast cancer risk markers, patients with luminal A tumors had an overall risk for 10-year ipsilateral breast recurrence (IBR) of 5.2%, compared with 10.5% for the luminal B subtype and 21.3% for the high-risk subtypes. In addition, a subanalysis of patients with clinical low-risk luminal A disease showed that the 10-year IBR was not significantly better with tamoxifen plus radiotherapy (RT) than with tamoxifen alone (5.0% vs. 1.3%, P = .42), Dr. Fei-Fei Liu of the Princess Margaret Cancer Centre in Toronto and associates reported (Journ. Clin. Onc. 2015 May 11 [doi:10.1200/JCO.2014.57.7999]).

“These results suggest that when luminal A subtype is combined with clinical and pathologic factors, a subgroup of patients with a low risk of IBR may be defined for whom the benefits of RT are small. However, omitting RT and using intrinsic subtyping and clinical factors is a substantial change in care. The breast cancer community would likely require additional prospective evidence before this becomes standard of practice,” the investigators wrote.

They looked at tissue samples from patients enrolled in the Toronto–British Columbia trial, in which older patients with node-negative breast cancer were randomly assigned to tamoxifen or tamoxifen plus radiotherapy. The samples were analyzed with a panel of six immunohistochemical (IHC) markers to identify whether intrinsic subtypes could predict radiotherapy benefit. The markers were estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor, and Ki-67.

Of the 501 samples analyzed, 265 were determined to be the luminal A subtype, 165 were luminal B, and the remaining 71 were high-risk subtypes, including luminal HER2, HER2 enriched, basal-like and triple negative.

In an exploratory analysis, the authors sought to identify women with a 10-year IBR risk below 5% who might be spared radiotherapy, and found that when they added clinicopathologic features to intrinsic subtyping, there was a subgroup of 151 low-risk luminal A patients with a 10-year 1BR rate of just 3.1%.

Canadian investigators have initiated a prospective, single-arm clinical trial open to women aged 55 or older with pT1N0 grade 1/2 luminal A breast cancer. The patients will undergo breast-conserving surgery and endocrine therapy without radiotherapy. The trial will be stopped if the projected risk of IBR exceeds 5%, Dr. Liu and colleagues said.

The study was supported by the Canadian Institutes of Health Research, the Guglietti Foundation, the Princess Margaret Cancer Foundation, the Campbell Family Institute for Cancer Research, and the Ministry of Health and Long-term Planning, Province of Ontario. Dr. Liu reported no conflicts of interest. Four of her coauthors reported having financial relationships with industry.

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